Bone and Body Comp: A Sub Study of the SECOND-LINE Study

HIV Clinical Trial

Official title:

Bone and Body Comp: A Sub Study of the SECOND-LINE Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01513122
• Other study ID #: 2L body comp sub-study
• Status: Completed
• Phase: Phase 4
• Start date: February 2010
• Est. completion date: August 2013

Study information

• Verified date: August 2019
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The use of anti HIV drugs (ART), and in particular a class of drugs known as nucleoside reverse transcriptase inhibitors (N(t)RTI), has been associated with changes in body fat and in particular loss of peripheral fat in the limbs. Low bone mineral density and osteoporosis are also common in HIV-infected patients. There appears to be some association between ART and bone loss, but this is poorly understood and requires further research. The SECOND-LINE study provides an opportunity to examine if a new anti-HIV drug (raltegravir) can result in greater increase in limb fat than a drug regimen containing N(t)RTI, which is currently standard of care. This study also provides an opportunity to examine if additional bone loss occurs with the second regimen of anti-HIV drugs and whether non-N(t)RTI regimens of ART used in second line therapy result in more or less bone loss than use of other classes of anti-HIV drugs such as protease inhibitors or N(t)RTI combinations.

It is hypothesized that subjects randomised into Raltegravir arm will demonstrate greater increases in limb fat and smaller reductions in bone density at the proximal femur over 48 weeks than those randomised into the control arm (LPV/r + 2-3N(t)RTIs).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: August 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Second-Line main study identifier: NCT00931463

Inclusion Criteria:

1. HIV-1 positive by licensed diagnostic test

2. Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)

3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for = 24 weeks

4. No change in antiretroviral therapy within 12 weeks prior to screening

5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (=7 days apart) HIV RNA results of > 500 copies/mL

6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors

7. Able to provide written informed consent

Exclusion Criteria:

1. The following laboratory variables:

• absolute neutrophil count (ANC) < 500 cells/µL

• hemoglobin < 7.0 g/dL

• platelet count < 50,000 cells/µL

• ALT > 5 x ULN

2. Pregnant or nursing mothers

3. Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen

4. Use of immunomodulators within 30 days prior to screening

5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)

6. Intercurrent illness requiring hospitalisation

7. Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator

8. Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study

9. Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Lopinavir / ritonavir
LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily
• 2-3N(t)RTI

• raltegravir
raltegravir 400mg 1 tablet twice daily.

Locations

Country	Name	City	State
Argentina	CEADI	Buenos Aires
India	YRGCare Medical Centre	Chennai
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
South Africa	JOSHA Research	Bloemfontein
South Africa	Desmond Tutu HIV Foundation	Cape Town
South Africa	Chris Hani Baragwanath Hospital	Soweto
Thailand	HIV-NAT Program on AIDS - Thai Red Cross	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Countries where clinical trial is conducted

Argentina,  India,  Malaysia,  South Africa,  Thailand, 

References & Publications (2)

Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, Phanuphak P, Ferret S, Cooper DA, Boyd MA; Second Line study team. Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line thera — View Citation

Martin A, Moore CL, Mallon PW, Hoy JF, Emery S, Belloso WH, Phanuphak P, Ferret S, Cooper DA, Boyd MA; Second-Line Study Team. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inh — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan		48 weeks
Primary	Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan		48 weeks
Secondary	Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan		48 weeks
Secondary	Mean Triglycerides Changes From Baseline to 48 Weeks		48 weeks
Secondary	Mean Total Cholesterol Changes From Baseline to 48 Weeks		48 weeks
Secondary	Mean Glucose Changes From Baseline to 48 Weeks		48 weeks